Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1989 Oct;8(10):3019–3027. doi: 10.1002/j.1460-2075.1989.tb08452.x

Human herpes virus-6 increases HIV-1 expression in co-infected T cells via nuclear factors binding to the HIV-1 enhancer.

B Ensoli 1, P Lusso 1, F Schachter 1, S F Josephs 1, J Rappaport 1, F Negro 1, R C Gallo 1, F Wong-Staal 1
PMCID: PMC401379  PMID: 2573513

Abstract

Human Herpes virus-6 (HHV-6) can co-infect with HIV-1 human CD4+ T-cells, leading to accelerated cell death, and factors in HHV-6-infected cells stimulate HIV-1 LTR directed gene expression. In this study, we have examined the mechanism of HIV-1 activation by HHV-6 and localized the cis-acting sequences of HIV-1 LTR responsive to trans-activation. Increased HIV-1 LTR directed gene expression is obtained in HIV-1 infected cells co-infected with HHV-6, or in HHV-6 infected cells co-transfected with the HIV-1 tat gene. Parallel increases of HIV-1-specific transcripts are seen by in situ hybridization in HHV-6/HIV-1 doubly infected cells as compared to single HIV-1 infection. Similarly, infection by HHV-6 increases the steady-state level of HIV-1 LTR mRNA that parallels CAT enzymatic activity, suggesting a transcriptional and/or post-transcriptional activation. Sequences necessary for HIV-1 LTR activation by HHV-6 are distinct from those required for that tat response and map to a region of the HIV-1 LTR from -103 to -48. The HIV-1 enhancer sequence (-105 to -80) is sufficient to confer HHV-6 inducibility to a heterologous promoter, and nuclear protein(s) activated or induced by HHV-6 infection specifically bind to the NF kappa B motifs of the HIV-1 enhancer region.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
3019

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ablashi D. V., Josephs S. F., Buchbinder A., Hellman K., Nakamura S., Llana T., Lusso P., Kaplan M., Dahlberg J., Memon S. Human B-lymphotropic virus (human herpesvirus-6). J Virol Methods. 1988 Sep;21(1-4):29–48. doi: 10.1016/0166-0934(88)90050-x. [DOI] [PubMed] [Google Scholar]
  2. Ablashi D. V., Lusso P., Hung C. L., Salahuddin S. Z., Josephs S. F., Llana T., Kramarsky B., Biberfeld P., Markham P. D., Gallo R. C. Utilization of human hematopoietic cell lines for the propagation and characterization of HBLV (human herpesvirus 6). Int J Cancer. 1988 Nov 15;42(5):787–791. doi: 10.1002/ijc.2910420526. [DOI] [PubMed] [Google Scholar]
  3. Arya S. K., Guo C., Josephs S. F., Wong-Staal F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Jul 5;229(4708):69–73. doi: 10.1126/science.2990040. [DOI] [PubMed] [Google Scholar]
  4. Arya S. K. Human and simian immunodeficiency retroviruses: activation and differential transactivation of gene expression. AIDS Res Hum Retroviruses. 1988 Jun;4(3):175–186. doi: 10.1089/aid.1988.4.175. [DOI] [PubMed] [Google Scholar]
  5. Ballard D. W., Böhnlein E., Lowenthal J. W., Wano Y., Franza B. R., Greene W. C. HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene. Science. 1988 Sep 23;241(4873):1652–1655. doi: 10.1126/science.241.4873.1652. [DOI] [PubMed] [Google Scholar]
  6. Buchbinder A., Josephs S. F., Ablashi D., Salahuddin S. Z., Klotman M. E., Manak M., Krueger G. R., Wong-Staal F., Gallo R. C. Polymerase chain reaction amplification and in situ hybridization for the detection of human B-lymphotropic virus. J Virol Methods. 1988 Sep;21(1-4):191–197. doi: 10.1016/0166-0934(88)90065-1. [DOI] [PubMed] [Google Scholar]
  7. Böhnlein E., Lowenthal J. W., Siekevitz M., Ballard D. W., Franza B. R., Greene W. C. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Cell. 1988 Jun 3;53(5):827–836. doi: 10.1016/0092-8674(88)90099-2. [DOI] [PubMed] [Google Scholar]
  8. Cross S. L., Feinberg M. B., Wolf J. B., Holbrook N. J., Wong-Staal F., Leonard W. J. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cell. 1987 Apr 10;49(1):47–56. doi: 10.1016/0092-8674(87)90754-9. [DOI] [PubMed] [Google Scholar]
  9. Cullen B. R. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986 Sep 26;46(7):973–982. doi: 10.1016/0092-8674(86)90696-3. [DOI] [PubMed] [Google Scholar]
  10. Davis M. G., Kenney S. C., Kamine J., Pagano J. S., Huang E. S. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8642–8646. doi: 10.1073/pnas.84.23.8642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Edery I., Petryshyn R., Sonenberg N. Activation of double-stranded RNA-dependent kinase (dsl) by the TAR region of HIV-1 mRNA: a novel translational control mechanism. Cell. 1989 Jan 27;56(2):303–312. doi: 10.1016/0092-8674(89)90904-5. [DOI] [PubMed] [Google Scholar]
  12. Efstathiou S., Gompels U. A., Craxton M. A., Honess R. W., Ward K. DNA homology between a novel human herpesvirus (HHV-6) and human cytomegalovirus. Lancet. 1988 Jan 2;1(8575-6):63–64. doi: 10.1016/s0140-6736(88)91049-5. [DOI] [PubMed] [Google Scholar]
  13. Folks T., Powell D. M., Lightfoote M. M., Benn S., Martin M. A., Fauci A. S. Induction of HTLV-III/LAV from a nonvirus-producing T-cell line: implications for latency. Science. 1986 Feb 7;231(4738):600–602. doi: 10.1126/science.3003906. [DOI] [PubMed] [Google Scholar]
  14. Franza B. R., Jr, Josephs S. F., Gilman M. Z., Ryan W., Clarkson B. Characterization of cellular proteins recognizing the HIV enhancer using a microscale DNA-affinity precipitation assay. 1987 Nov 26-Dec 2Nature. 330(6146):391–395. doi: 10.1038/330391a0. [DOI] [PubMed] [Google Scholar]
  15. Gendelman H. E., Phelps W., Feigenbaum L., Ostrove J. M., Adachi A., Howley P. M., Khoury G., Ginsberg H. S., Martin M. A. Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759–9763. doi: 10.1073/pnas.83.24.9759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gimble J. M., Duh E., Ostrove J. M., Gendelman H. E., Max E. E., Rabson A. B. Activation of the human immunodeficiency virus long terminal repeat by herpes simplex virus type 1 is associated with induction of a nuclear factor that binds to the NF-kappa B/core enhancer sequence. J Virol. 1988 Nov;62(11):4104–4112. doi: 10.1128/jvi.62.11.4104-4112.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gowans E. J., Baroudy B. M., Negro F., Ponzetto A., Purcell R. H., Gerin J. L. Evidence for replication of hepatitis delta virus RNA in hepatocyte nuclei after in vivo infection. Virology. 1988 Nov;167(1):274–278. doi: 10.1016/0042-6822(88)90078-5. [DOI] [PubMed] [Google Scholar]
  19. Hahn B. H., Shaw G. M., Arya S. K., Popovic M., Gallo R. C., Wong-Staal F. Molecular cloning and characterization of the HTLV-III virus associated with AIDS. Nature. 1984 Nov 8;312(5990):166–169. doi: 10.1038/312166a0. [DOI] [PubMed] [Google Scholar]
  20. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Heisig V., Benter T., Josephs S. F., Sadaie M. R., Okamoto T., Gallo R. C., Wong-Staal F. Interaction of viral and cellular factors with the HTLV-III LTR target sequences in vitro. Haematol Blood Transfus. 1987;31:423–429. doi: 10.1007/978-3-642-72624-8_90. [DOI] [PubMed] [Google Scholar]
  22. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  23. Josephs S. F., Salahuddin S. Z., Ablashi D. V., Schachter F., Wong-Staal F., Gallo R. C. Genomic analysis of the human B-lymphotropic virus (HBLV). Science. 1986 Oct 31;234(4776):601–603. doi: 10.1126/science.3020691. [DOI] [PubMed] [Google Scholar]
  24. Josephs S. F., Wong-Staal F., Manzari V., Gallo R. C., Sodroski J. G., Trus M. D., Perkins D., Patarca R., Haseltine W. A. Long terminal repeat structure of an American isolate of type I human T-cell leukemia virus. Virology. 1984 Dec;139(2):340–345. doi: 10.1016/0042-6822(84)90379-9. [DOI] [PubMed] [Google Scholar]
  25. Kaufman J. D., Valandra G., Roderiquez G., Bushar G., Giri C., Norcross M. A. Phorbol ester enhances human immunodeficiency virus-promoted gene expression and acts on a repeated 10-base-pair functional enhancer element. Mol Cell Biol. 1987 Oct;7(10):3759–3766. doi: 10.1128/mcb.7.10.3759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kenney S., Kamine J., Markovitz D., Fenrick R., Pagano J. An Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1652–1656. doi: 10.1073/pnas.85.5.1652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kenney S., Natarajan V., Salzman N. P. Mapping 5' termini of JC virus late RNA. J Virol. 1986 Apr;58(1):216–219. doi: 10.1128/jvi.58.1.216-219.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Knight D. M., Flomerfelt F. A., Ghrayeb J. Expression of the art/trs protein of HIV and study of its role in viral envelope synthesis. Science. 1987 May 15;236(4803):837–840. doi: 10.1126/science.3033827. [DOI] [PubMed] [Google Scholar]
  29. Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lawrence J. B., Singer R. H. Intracellular localization of messenger RNAs for cytoskeletal proteins. Cell. 1986 May 9;45(3):407–415. doi: 10.1016/0092-8674(86)90326-0. [DOI] [PubMed] [Google Scholar]
  31. Lusso P., Ensoli B., Markham P. D., Ablashi D. V., Salahuddin S. Z., Tschachler E., Wong-Staal F., Gallo R. C. Productive dual infection of human CD4+ T lymphocytes by HIV-1 and HHV-6. Nature. 1989 Jan 26;337(6205):370–373. doi: 10.1038/337370a0. [DOI] [PubMed] [Google Scholar]
  32. Lusso P., Markham P. D., Tschachler E., di Marzo Veronese F., Salahuddin S. Z., Ablashi D. V., Pahwa S., Krohn K., Gallo R. C. In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6). J Exp Med. 1988 May 1;167(5):1659–1670. doi: 10.1084/jem.167.5.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Hayward G. S., Pitha P. M. Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7408–7412. doi: 10.1073/pnas.84.21.7408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Pitha P. M. Herpes simplex virus type-1 can reactivate transcription of latent human immunodeficiency virus. Nature. 1987 Jan 1;325(6099):67–70. doi: 10.1038/325067a0. [DOI] [PubMed] [Google Scholar]
  35. Nabel G. J., Rice S. A., Knipe D. M., Baltimore D. Alternative mechanisms for activation of human immunodeficiency virus enhancer in T cells. Science. 1988 Mar 11;239(4845):1299–1302. doi: 10.1126/science.2830675. [DOI] [PubMed] [Google Scholar]
  36. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  37. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  38. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  39. Salahuddin S. Z., Ablashi D. V., Markham P. D., Josephs S. F., Sturzenegger S., Kaplan M., Halligan G., Biberfeld P., Wong-Staal F., Kramarsky B. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986 Oct 31;234(4776):596–601. doi: 10.1126/science.2876520. [DOI] [PubMed] [Google Scholar]
  40. Seto E., Yen T. S., Peterlin B. M., Ou J. H. Trans-activation of the human immunodeficiency virus long terminal repeat by the hepatitis B virus X protein. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8286–8290. doi: 10.1073/pnas.85.21.8286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Siekevitz M., Josephs S. F., Dukovich M., Peffer N., Wong-Staal F., Greene W. C. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Science. 1987 Dec 11;238(4833):1575–1578. doi: 10.1126/science.2825351. [DOI] [PubMed] [Google Scholar]
  42. Sodroski J., Patarca R., Rosen C., Wong-Staal F., Haseltine W. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985 Jul 5;229(4708):74–77. doi: 10.1126/science.2990041. [DOI] [PubMed] [Google Scholar]
  43. Tong-Starksen S. E., Luciw P. A., Peterlin B. M. Human immunodeficiency virus long terminal repeat responds to T-cell activation signals. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6845–6849. doi: 10.1073/pnas.84.19.6845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wildeman A. G., Sassone-Corsi P., Grundström T., Zenke M., Chambon P. Stimulation of in vitro transcription from the SV40 early promoter by the enhancer involves a specific trans-acting factor. EMBO J. 1984 Dec 20;3(13):3129–3133. doi: 10.1002/j.1460-2075.1984.tb02269.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zagury D., Bernard J., Leonard R., Cheynier R., Feldman M., Sarin P. S., Gallo R. C. Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science. 1986 Feb 21;231(4740):850–853. doi: 10.1126/science.2418502. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES